The first-rate ship HMS Royal George was laid down as Royal Anne in 1746 but renamed in honor of the reigning monarch George II before her launch ten years later. The first warship to exceed 2,000 tons burden, Royal George was commissioned at the start of the Seven Years' War with France and joined the Western Squadron in blockading the port of Brest and Quiberon Bay. On November 9, 1759, the British fleet was blown off station, and Vice Admiral Hubert de Brienne, Comte de Conflans, seized the opportunity to sortie from Brest with twenty-one ships of the line. This he did the same day that Admiral Sir Edward Hawke left Torbay, beating against the westerlies to regain his station. On the afternoon of November 20, 1759, the two fleets spotted each other off Brest, and Hawke ordered his ships to "form as you chase." Conflans decided to return to Brest, and despite the treacherous shoals and reefs of Quiberon Bay, Hawke ordered his ships to follow the French. As Conflans later wrote, "I had no reason to believe that if I went in first with my ships the enemy would dare follow, in spite of his superiority [of two ships] which must anyway restrict his movements."

The ensuing destruction of the French fleet was decisive. Thésée foundered when water rushed in through her lower gun ports, and Héros struck to HMS Magnanime (a French prize of 1748). As Royal George came up with Conflans's flagship Soleil Royal (80 guns), the French Superbe interposed herself but sank after one broadside from Hawke's flagship. The French Formidable also struck before darkness fell and Hawke ordered his fleet to anchor. The next morning revealed HMS Resolution and Essex driven ashore on Le Four shoal, but Soleil Royal was lost on Rouelle shoal and three other French ships were damaged beyond repair.

Hawke was knighted for his action, and Royal George spent the rest of the war on blockade duty off Brest. Peace came in 1763, and between that year and 1778, the Royal Navy laid up ninety-seven ships of the line, Royal George among them. When France threw in her lot with the American colonists and allied with Spain, Royal George recommissioned. In July 1778, she was under command of Sir Charles Hardy in his ignominious withdrawal before the combined Franco-Spanish fleet as it advanced up the Channel. (Sailors in Royal George are said to have blindfolded the figureheads, popularly believed to represent the former king, so that "George II should never see an English Fleet chased up their own channel.") In the event, Admiral Louis Guillouet, Comte d'Orvilliers, withdrew of his own accord, and England was spared further anxiety about the biggest invasion to threaten since the Spanish Armada in 1588.

At the end of 1779, Royal George sailed with Admiral Sir George Rodney's fleet to relieve Gibraltar and took part in the capture of two Spanish convoys, one guarded by nine ships under Admiral Don Juan de Langara; seven of these were captured or sunk. In 1782, she was part of another fleet, under Admiral Lord Howe, assembled for the permanent relief of Gibraltar. The ships were anchored at Spithead, taking on supplies, when on August 29 Royal George was being heeled at a slight angle to make some minor repairs below the waterline. At the same time, casks of rum were being loaded aboard and the lower deck gunports were not properly secured. At about 0920 the ship suddenly rolled over on her beam ends, filled with water, and sank, taking with her 800 people, including as many as 300 women and 60 children who were visiting the ship. A subsequent court-martial acquitted the ship's officers and crew (most of whom were dead) of any wrongdoing, and blamed the accident on the "general state of decay of her timbers."

Several attempts were made to salvage the ship. In 1783, William Tracey succeeded in moving the ship slightly before the Admiralty decided to abandon the project. In 1834, the pioneering diver Charles Deane recovered thirty guns before his work was interrupted to investigate a nearby wreck that turned out to be Mary Rose. The remains of Royal George were eventually blown up by Royal Engineers in the early 1840s.